PROJECT SUMMARY Menopause is associated with a decline in estradiol (E2) that coincides with a significant accumulation of abdominal adipose tissue (AT). Yet, little is known about whether the loss of estradiol alters depot-specific AT expansion and function in a manner that promotes abdominal adiposity. It is unknown whether the increased abdominal AT mass that accompanies menopause is due to increased adipogenesis or other mechanisms such as increased hypertrophy or altered lipid storage. Our studies of premenopausal versus estrogen-depleted, postmenopausal women will allow us to examine estrogen withdrawal as a mechanism for adipogenesis (Aim 1) and altered AT function (Aim 2) within the subcutaneous abdominal and femoral depots that has not been explored. Our overarching hypothesis is that E2 loss with menopause promotes abdominal adipogenesis and impair AT function. We would be the first to identify potential novel depot-specific AT pathways in estrogen- depleted, postmenopausal women to explain the accumulation in abdominal adiposity that occurs with menopause. Knowledge gained from our studies will allow us to design and implement more targeted approaches for intervention that prevent abdominal AT accumulation in women. The acquired skills and career development plan in this K01 proposal will allow me to emerge as an independent, NIH-funded scientist in women’s health research that integrates treatments to reduce abdominal adiposity and improve metabolic health in midlife women.